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R Ismail

Publications and source records attributed to R Ismail.

At least 19 recordsLinked to original sources
PubMed2001

Validation of a high-performance liquid chromatography method for tramadol and o-desmethyltramadol in human plasma using solid-phase extraction.

An HPLC system using solid-phase extraction and HPLC with UV detection has been validated in order to determine tramadol and o-desmethyltramadol (M1) concentrations in human plasma. The method developed was selective and linear for concentrations ranging from 50 to 3,500 ng/ml (tramadol) and 50 to 500 ng/ml (M1) with mean recoveries of 94.36 +/- 12.53% and 93.52 +/- 7.88%, respectively. Limit of quantitation (LOQ) was 50 ng/ml. For tramadol, the intra-day accuracy ranged from 95.48 to 114.64% and the inter-day accuracy, 97.21 to 103.24%. Good precision (0.51 and 18.32% for intra- and inter-day, respectively) was obtained at LOQ. The system has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.

Analgesics, Opioid↗
PubMed2001

Heterogeneity of the CYP2D6 gene among Malays in Malaysia.

BACKGROUND: Although Malays shared an origin with Chinese, their evolution saw substantial divergences. Phenotyping studies suggested that they differed in CYP2D6 polymorphism, with higher PM prevalence but lesser right-shift for debrisoquine MRs. OBJECTIVE: To study the genotype distribution of CYP2D6 among the Malays in Malaysia. METHOD: We obtained DNA from 107 Malays and used PCR to determine common CYP2D6 alleles. RESULT: CYP2D6*1 occurred at a frequency of 36.0%, duplicated gene, 0.93%, CYP2D6*4, 2.8%, CYP2D6*5, 5.1%, CYP2D6*9, 3.3%, CYP2D6*10, 49.5% and CYP2D6*17, 0.5%. The findings of CYP2D6*17 and CYP2D6*9 were novel for Asia. The frequency for CYP2D6*10 was lower than in other Asian races. The most frequent genotypes were CYP2D6*1/*10 at 39.3%. Two subjects had genotypes that predicted PM phenotype, 35% showed genotypes that predicted intermediate metabolizers and one subject had a genotype that predicted ultra-rapid metabolism. CONCLUSION: The genetic polymorphism of CYP2D6 in Malays is different from Chinese and Far Eastern races. They may be intermediate between East Asians and Caucasians in CYP2D6 activity. Further study in relation to the evolution of races and disease prevalence may help to identify the contributions of the polymorphism in alleged susceptibility to diseases apart from delineating its contributions to ethnic differences in the pharmacology of CYP2D6 drugs.

Adolescent↗
PubMed2000

Stroke.

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Acute Disease↗
PubMed2000

CYP2D6 phenotypes among Malays in Malaysia.

BACKGROUND: Although they originated from China, Malays have undergone a lot of intermarriages. A study suggested that CYP2D6 poor metabolism (PM) phenotype was more common in Malays compared to Chinese. CYP2D6 is highly polymorphic and is involved in the metabolism of many drugs and has been implicated in some environmentally-induced diseases. It is therefore useful to further study this polymorphism in Malays. OBJECTIVE: To study debrisoquine metabolism phenotypes in healthy Malay volunteers. METHOD: We administered debrisoquine to 51 Malays and used HPLC to measure urinary debrisoquine and 4-hydroxy debrisoquine to calculate debrisoquine metabolic ratios (MR). RESULTS: Debrisoquine MR varied widely and with probit analysis we were able to identify population subsets. Although the frequency distribution for the MR showed a right shift, the shift was less than that reported for the Chinese population. We also found 2 poor metabolizers and one ultra rapid metaboliser in the population. CONCLUSION: The genetic polymorphism of debrisoquine in Malays differs from that in the Chinese. Both their PM prevalence and their MR distribution suggest that they are intermediate between Europeans and Chinese in relation to this polymorphism. Studies to compare CYP2D6 genotypes between them and related races would be useful to further define these differences.

Adult↗
PubMed2000

Ethnic differences in response to non-selective beta-blockade among racial groups in Malaysia.

OBJECTIVE: To determine whether racial differences in response to blockade of beta receptors occur among racial groups in Malaysia that are the Malays, Indians and Chinese. SUBJECTS, MATERIALS AND METHOD: 35 healthy male volunteers representing the 3 main racial groups in Malaysia (12 Malays, 12 Chinese and 11 Indians) were studied in a randomized, placebo-controlled, crossover and single-blind design. Propranolol 80 mg 12-hourly was given orally for 48 hours. Six hours after the last dose subjects attended an exercise session where resting and exercise heart rate, blood pressure, plasma potassium and glucose levels, resting FEV1 and plasma propranolol concentrations were recorded. RESULTS: No significant difference in plasma propranolol (mean +/- SEM) levels was seen between races six hours after the last dose (Malays, 59.7 +/- 8.8 ng/ml, Indians, 67.6 +/- 19.3 ng/ml, Chinese, 58.4 +/- 7.9 ng/ml). Chinese were least sensitive to the bradycardic and hypotensive effects of propranolol at rest and exercise. Indians and Malays had significant reduction of supine systolic blood pressure with propranolol but not Chinese. Comparison of percentage reductions of systolic blood pressure at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.022). Similarly, comparison of percentage reductions of heart rate at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.040). Average change in potassium concentrations at peak exercise and recovery showed the Indians to have significantly higher increase in potassium levels with propranolol compared to the Malays (p = 0.038). However, no significant interethnic difference was seen in the reduction of glucose levels at rest, peak exercise or recovery. Also, no significant interethnic difference was seen in reduction of FEV1 values. CONCLUSION: We, therefore, conclude that ethnic differences in response to blockade of beta-receptors exist among racial groups in Malaysia. These differences were seen at similar plasma drug levels between races suggesting ethnic differences in drug sensitivity, rather than differences in drug disposition.

Adrenergic beta-Antagonists↗
PubMed1999

Mucocutaneous manifestations of HIV infection: a retrospective analysis of 145 cases in a Chinese population in Malaysia.

BACKGROUND: Mucocutaneous lesions directly related to human immunodeficiency virus (HIV) infection usually present as initial manifestations of immune deficiency. The most common mucocutaneous lesions are Kaposi's sarcoma, histoplasmosis, oro-esophageal candidiasis, oral hairy leukoplakia, and, in Asia, Penicillium marneffei infection. Non-HIV-related skin lesions, such as psoriasis, seborrheic dermatitis, and nodular prurigo, may be the initial presentation among HIV infected patients attending outpatient clinics. METHODS: A retrospective analysis was performed on 145 HIV-positive Malaysians of Chinese descent from two centers at the University Hospital Kuala Lumpur (UHKL) and the General Hospital Kuala Lumpur (GHKL) from March 1997 to February 1998. Demographic data and clinical data were analyzed. RESULTS: The analysis showed that 104 out of 145 patients had mucocutaneous disorders (71.7%). In the study, there were 100 men (96.2%) and four women (3.8%). The majority of patients were in the age group 20-50 years. The patients who presented with mucocutaneous disease also had low CD4+ T-lymphocyte counts and most had acquired immunodeficiency syndrome (AIDS) defining illness. The number of cases with generalized hyperpigmentation was very high in the group (35.9%), followed by nodular prurigo (29.7%) and xerosis (27.6%). Seborrheic dermatitis was seen in 20.7% of cases, with psoriasis in 8.3%. The most common infections were oral candidiasis (35.9%), tinea corporis and onychomycosis (9.7%), and herpes infection (5.5%); however, mucocutaneous manifestations of Kaposi's sarcoma were rare. CONCLUSIONS: The results suggest that mucocutaneous findings are useful clinical predictors of HIV infection or signs of the presence of advanced HIV infection.

Adult↗
PubMed1998

Cloning and expression of the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA.

Using a cDNA probe from the rat 24-hydrovitamin D3 24-hydroxylase, the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA has been isolated from a chicken kidney lambda gt11 library. The high degree of similarity with the mammalian 24-hydroxylase cDNAs strongly supports the belief that it is the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA. The deduced amino acid sequences are also very well conserved and 325 of them are identical among the four known 25-hydroxyvitamin D3 24-hydroxylases. This cDNA expressed in E. coli produces 24-hydroxylase activity.

Amino Acid Sequence↗
PubMed1998

Dynamic assessment of parathyroid function in acute malaria.

OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers. DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.

Acute Disease↗
PubMed1998

Chloramphenicol in children: dose, plasma levels and clinical effects.

Despite concerns about adverse effects, chloramphenicol (CMC) continues to be used in certain situations and, due to its low therapeutic index and variable pharmacokinetics, therapeutic drug monitoring (TDM) is often recommended. At our centre, CMC finds applications in typhoid and meningitis and TDM is routinely performed. Elsewhere in Malaysia, however, CMC is used without TDM. We therefore decided to evaluate our TDM for CMC in relation to its roles in CMC therapy in children, who constitute most of our patients. Our objective was also to develop strategies to improve our TDM for CMC use. Data were collected from 168 children given CMC for various indications and monitored by the TDM service. Plasma CMC was determined by HPLC and used to adjust doses to maintain concentrations within a range of 10-25 micrograms/ml. Outcomes measured included daily temperatures and haematological indices. Daily doses and plasma CMC varied greatly. Doses averaged 40.5 mg/kg for neonates and 75.5 for older children. Average peak concentrations were therapeutic in 60% and trough in 42%. Average duration of fever was 6.3 days and it was unaffected by plasma CMC. Typhoid was eradicated in 97% but nine children with other diagnoses died. Side-effects were confined to mild reversible haematological abnormalities which developed in 11% of children at plasma concentrations which tended to be high. We conclude that CMC remains useful in children with typhoid. Its use for other indications, however, should be reviewed. Routine TDM for CMC is probably not warranted, at least until a clearer role is defined by well designed prospective studies.

Anemia↗
PubMed1998

HIV/AIDS in Malaysia.

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Acquired Immunodeficiency Syndrome↗
PubMed1997

Therapeutic drug monitoring of gentamicin: a 6-year follow-up audit.

BACKGROUND AND OBJECTIVE: In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic. In this study we report on a 6-year follow-up audit since our first assessment of the service. METHOD: Records of 733 requests for gentamicin monitoring were reviewed. RESULTS: Of the 592 patients involved, 39% were neonates and 42% were adults. Peak gentamicin concentrations were within the therapeutic range in 65% of the patients at first monitoring and 79% of the corresponding trough concentrations were within the non-toxic range. After dosage adjustment, 81% of the peak concentrations were within the therapeutic range and trough concentrations rose to levels regarded as toxic in 7% of patients. In patients with therapeutic peak concentrations at the first monitoring point, the average duration of gentamicin therapy was statistically shorter than in those patients who failed to achieve a therapeutic peak concentration. The distribution of gentamicin peak and trough concentrations in terms of therapeutic ranges were also better than those found in 1990. CONCLUSION: TDM for gentamicin is well accepted in HUSM and its application has contributed to improved gentamicin administration. Furthermore, our physicians are now able to choose more appropriate dosage regimens for their patients because the majority of gentamicin concentrations attained even at the first monitoring were within the therapeutic range.

Adult↗
PubMed1995

Composition and preliminary evaluation of a hydrolyzed rice-based oral rehydration solution for the treatment of acute diarrhea in children.

OBJECTIVE: The purpose of this study was to experimentally develop and clinically evaluate the safety and potential usefulness of a rice-based, short glucose polymer oral rehydration solution (ORS), Amylyte, in the treatment of acute diarrhea. Amylyte has a similar osmolality but a higher caloric density than the WHO ORS. METHODS: Different amounts of rice were cooked in 500 ml of water containing salts (1.5 g NaCl, 600 mg KCl, and 150 mg CaCl2) with varying amounts of thermophilic amylase (252,500 modified Wohlgemuth units). Amylase (25 mg) thinned the gluey rice water when 100 g of rice was cooked in 500 ml of water for 10 minutes. The volume of the resultant supernatant (Amylyte) was approximately 250 ml. A two-part, clinical case study was performed. In study 1, 12 children with diarrhea and mild dehydration were studied to determine the safety of Amylyte. In study 2, Amylyte and the WHO ORS were given to 24 and 31 male children with acute diarrhea and moderate to severe dehydration, respectively. RESULTS: 92-96% of the rice amylose and amylopectin were converted to short polymers of glucose (3-9 molecules of glucose). The osmolality of 7,994 packages used to make the Amylyte solution ranged between 277-340 mOsm/kg. The mean electrolyte composition was Na+ = 68 mEq/L, K+ = 20 mEq/L, Cl = 73 mEq/L, the caloric density 425 kcal/L and rice proteins 0.7 g/L. In study 1, 12 children with diarrhea and mild dehydration were rehydrated successfully with Amylyte ORS and the diarrhea ceased within 48 hours. None developed clinical features of carbohydrate intolerance. In study 2, an open-label clinical case study, children with acute diarrhea given Amylyte ORS had significantly less stool output than children given the WHO ORS. CONCLUSIONS: Amylyte ORS has the advantages of a higher caloric density than the WHO ORS and shares a simple preparation of appropriate osmolality and electrolyte composition. It can safely and effectively rehydrate children with acute diarrhea and dehydration.

Acute Disease↗
PubMed1995

High-calorie, rice-derived, short-chain, glucose polymer-based oral rehydration solution in acute watery diarrhea.

In this study, we have compared the effects of the World Health Organization oral rehydration solution (WHO ORS) and an ORS containing short polymers of glucose (Amylyte ORS) at a high caloric density (five times) and comparable osmolality, on stool output, duration of diarrhea, weight gain and fluid and electrolyte balance, in randomized, open-labeled, controlled clinical trials in five centers. A total of 198 male children (4 months to 10 years) with acute diarrhea ( <72 h after onset) were assigned by random allocation to either WHO ORS or Amylyte ORS at five centers in Asia. Children were stratified according to grade of dehydration (mild, moderate or severe) and the initial purging rates during the first 6 h (low ( < 2 ml/kg/h), moderate (2-5 ml/kg/h) and high ( > 5 ml/kg/h) purgers). The clinical characteristics of the children in the two treatment groups were comparable. Amylyte ORS reduced stool volumes significantly in children with severe dehydration (285.4 +/- 74.2 versus 75.5 +/- 20.0 ml/kg; p < 0.05) and in children with a high initial purging rate (200.3 +/- 42.8 versus 130.5 +/- 9.1 ml/kg; p < 0.05). This was accompanied by a significant (276.4 +/- 14.6 versus 227.6 +/- 11.8 ml/kg; p < 0.01) reduction in ORS requirements in the Amylyte ORS treated group, the effect being greatest in children with severe dehydration (491.5 +/- 108.5 versus 155.7 +/- 27.3 ml/kg; p < 0.01) or high initial purging rates (394.2 +/- 66.2 versus 316.8 +/- 34.8 ml/kg; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

HIV infection in Malaysia: a report of cases seen at the University Hospital, Kuala Lumpur.

The spread of HIV infection into Malaysia is estimated to have occurred in the early 1980's. The first case of AIDS was reported here in 1986. As of March 31, 1994, the numbers have increased to 8049 HIV positive individuals detected in the country. The risk behaviours among those tested positive were intravenous drug use in 77.2%, sexual transmission in 4.5%, while the remainder are still under investigation. Pediatric AIDS constitutes 0.2% of positives. The high prevalence among intravenous drug users (IVDU) is likely to be due to mandatory testing for HIV upon entry to rehabilitation centres. The trend of HIV infection in this country seems to be highest amongst the intravenous drug users. The increasing number of HIV infected prostitutes and heterosexuals in our population is worrying. Since 1986, a total of 104 HIV positive individuals have been treated at the University Hospital, Kuala Lumpur, Malaysia. Of these, 25 have died and of those still alive, 5 have symptomatic disease. The most common AIDS-defining illness is Pneumocystis carinii pneumonia. Education programmes have been developed targeting the various high risk groups and the general population.

Adolescent↗
PubMed1994

cDNA cloning and characterization of a vitamin D3 hydroxylase-associated protein.

We previously reported the generation of monoclonal antibodies which immunoprecipitate a fraction of the total chick kidney 1,25-dihydroxyvitamin D3-24R-hydroxylase activity. These antibodies were used to screen a chick kidney lambda gt11 cDNA library resulting in the isolation of a full-length cDNA encoding a protein that is not the 1,25-dihydroxyvitamin D3-24R-hydroxylase but another protein we term the vitamin D3 hydroxylase-associated protein (VDHAP). The deduced amino acid sequence agreed with an NH2-terminal amino acid sequence from the isolated VDHAP. Gene and protein bank search did not identify homology to known sequences or functional domains in the VDHAP cDNA. VDHAP mRNA levels are not altered by conditions which either induce 1,25-dihydroxyvitamin D3-24R-hydroxylase activity (78-fold) or 25-hydroxyvitamin D3-1 alpha-hydroxylase activity (30-fold). Northern analysis of poly(A)+ RNA from chick tissues revealed VDHAP only in kidney. Cellular fractionation experiments demonstrated that VDHAP and the 25-hydroxyvitamin D3-1 alpha-hydroxylase are colocalized in the inner membrane of mitochondria. The VDHAP antibody immunoprecipitates 14% of the total 1,25-dihydroxyvitamin D3-24R-hydroxylase activity (7-fold over background) and immunoprecipitates 21% of the total 25-hydroxyvitamin D3-1 alpha-hydroxylase activity (2-fold over background). VDHAP is a novel chick kidney-specific inner membrane protein of mitochondria, which associates with a fraction of the 1,25-dihydroxyvitamin D3-24R-hydroxylase and 25-hydroxyvitamin D3-1 alpha-hydroxylase.

Amidohydrolases↗
PubMed1994

Pharmacokinetics of phenytoin in routine clinic patients in Malaysia.

We estimated individual and population Michaelis-Menten pharmacokinetic parameters for phenytoin (DPH) in epileptic patients attending our neurology clinic using the computer programme. OPT. Our results agreed well with literature values but were lower than those we obtained earlier in a smaller number of patients. The Km was independent of age, weight and sex but there was a weak, correlation between Vm and body weight. We conclude that the use of population Vm and Km in normograms could lead to errors in DPH dose estimations as they correlated very poorly with patient characteristics. OPT was easy to use and sufficiently accurate for deriving dose estimates in routine patients. Its use would enable practitioners to generate their patients' own parameters for use in individual dosage adjustments. The estimates can subsequently be updated as more data become available.

Adolescent↗